April 16, 2010, 2010

Elliott K. Lee MD, FRCP(C)

Staff Psychiatrist

Anxiety Disorders Clinic

Royal Ottawa Mental Health Centre

Anxiety results from an unknown internal stimulus, or is inappropriate or excessive when compared to the existing external stimulus.

It is an expected, normal and transient response to stress; may be a necessary cue for adaptation and coping (future event)

Different from Fear:sense of dread/foreboding that occurs in response to external threatening event.

Pathologic anxiety1.Autonomy: i.e. Minimal/no recognizable

environmental trigger2.Intensity – exceeds tolerance capacity3.Duration – persistent, not transient4.Behaviour – impairs coping:

results in disabling behavioural strategies – avoidance, withdrawal

Physical symptoms:- autonomic arousal – tachycardia, tachypnea, diaphoresis, diarrhoea, light headedness

Affective symptoms:Mild Severeedginess terror, feeling

loss of control, dying

BehaviourAvoidance, or compulsions (“compensatory”)

Cognitions – worry, apprehension, obsessions

Anxiety disorders arePrevalent , real, serious, treatable

Anxiety disorders are not

Signs of personal weakness

Nutt et al. In: Handbook of Anxiety and Fear 2008

Central noradrenergic system (NE):locus coeruleus (LC)– major source of brain’s adrenergic innervation. E.g. – stimulate LC – get panic attacks; block LC – decrease

Gamma Amino Butyric Acid (GABA) systemEspecially – septohippocampal areas – mediate generalized anxiety, worry, vigilance- BDZ bind to GABA receptors; reduce vigilance

Serotonergic system (5-HT)Modulate above 2 systems – explains efficacy of multiple clinical interventions – SSRIs, SNRIs, GABA agents, CBT

Psychopharmaology for anxiety disorders is based on those neurotransmitter systems:1) Norepinephrine

TCAs, Prazosin2) GABA

Benzodiazepines, anticonvulsants3) Serotonergic (5-HT) modulation

- SSRIs, SNRIs, TCAs

Limbic cortex

Periaqueductal Gray matter

Brain Stem

Ventral Tegmental Area

Hippocampus

Amygdala

Nucleus accumbens

Orbitofrontal cortex

State anxietyAn interruption of one’s emotional state- become restless, agitated, and then may react/overreact to external stimuli- high state anxiety is unpleasant – pts may seek out “adaptive” behaviours to alleviate this.

Trait anxiety“Stable aspect of personality”- may worry all the time, even with “normal stimuli”, then when there’s a real threatening stimuli – may worry even more

Normal healthy ptsvs.

Healthy pts with high trait anxiety

(Stait Trait Anxiety Inventory (STAI))

Shown - fearful faces- neutral faces- fearful+neutral faces- neutral+neutral faces

Etkin A. et al. Neuron, 2004

Etkin A. et al. Neuron, 2004

Conscious awareness of fearful face- dorsal region of amygdala activated in all subjects

Unconscious (masked) awareness fearful face- basolateral amygdala activated (high trait anixety pts)

Analyzed activation of amygdala (fMRI)

Focus on information processing and behavioural reactions

Faulty cognitions-e.g. Overprediction of likelihood/degree of catastrophe

Attempts to neutralize anxiety – e.g. With avoidance, compulsive behaviour, paradoxically “lock in” or reinforce anxiety►chronic arousal and anticipatory anxiety

Automatic thoughts/Feelings:I am foolish, I am incompetent, I am not loveable

Behaviour: RUN!

Reinforcement: I have not dated; good people don’t like me; I am foolish, I am incompetent, I am not loveable

Single person sees attractive person

Automatic thoughts/Feelings: that person is attractive, I am a good person. Maybe we can be a good match. Let’s find out

Behaviour: Initiate conversation***

Reinforcement: Attractive person seemed to enjoy talking to me. Maybe I have something to offer in a relationship

Cognitive Behavioural Therapy (CBT) is based on these notions

Replace anxiogenic thoughts and behaviours with positive ones.

World viewSelf View

Anxiety = threat to the ego; signals are elicited because current events have similarities (symbolic or actual) to threatening developmental experiences (traumatic anxiety)

Object relations theorists emphasize the use of internalized objects to maintain affective stability under stress

Ms. Anxietas – 23-year-old engaged grad student complains of periodic episodes of intense anxiety, and chronic fears about dying

Ruminates about her own age, and subsequent death, then to her parents.

Fears impair her sleep, and ability to function in her studies.

In therapy – issues of death are explored – the therapist comments concerns about living contribute to fears of death; “could anything be going on in her life that might contribute to her anxiety?”

“It’s not about my fiancee being stationed overseas!”....she cries....therapist offers her a tissue, but she declines

Therapist asks “Why did you decline tissue?”She replies – she thought it would be a sign of

weakness.They go on to explore, how everyone comes to her

for help, but she could not acknowledge she needed help from others.

Revealed significant issues with anger – but feared that her anger would explode and drive others away.

Further exploration – reveals she had a great deal of anger towards her father, that she had been unable to express

Unconscious concern – was that her anger would be so explosive it would destroy him.

After 2 months of therapy – Ms. Anxietas gained greater mastery over her fears

Began to understand the impact of her anger and her fears of being abandoned and alone.

Defensive function of anxiety may be to distract patient form more disturbing or underlying concerns.

Gabbard, GO. Psychodynamic Psychiatry in Clinical Practice, 2000

Panic Disorder without AgoraphobiaPanic Disorder with AgoraphobiaAgoraphobia without history of Panic DisorderSpecific PhobiaSocial PhobiaObsessive-Compulsive DisorderAcute Stress DisorderPosttraumatic Stress DisorderGeneralized Anxiety DisorderAnxiety Disorder Due to General Medical

Condition or Substance-Induced Anxiety DisorderAnxiety Disorder NOS

Somers et al. Can J Psychiatry 2006

9282 pts – english speaking12 month prevalence of numerous psychiatric

disordersAny psychiatric disorder 26.2%Any anxiety disorder 18.1%

Specific phobia (8.7%)

Social phobia (6.8%)

PTSD (3.5%)

GAD (3.1%)

Panic (2.7%)

OCD (1%)

5

10

Per

cent

age

(%)

Kessler et al. Arch Gen Psychiatry, 2005

Persistent and irrational fear of certain objects or situations

Exposure provokes anxiety/panic responseRecognized as excessive or unreasonablePhobic object/situation avoided or endured

with intense anxiety or distressSignificant interference or marked distress

Types: animals/insects, natural environment, blood/injury, situational, other

Most common anxiety disorderMarked and persistent fear of clearly discernible

circumscribed objects or situationsExposure almost invariably provokes anxietyFear is recognized as excessive or unreasonable

(though children may not)Phobic stimulus is avoided, or tolerated with

dreadAvoidance/fear leads to significant distress or

interference with social/occ functioningIn children – should persist >6 m

Biopsychosocial- Bio- Medications – generally not helpful.

BDZs – may provide some temporary relief (e.g. For flying etc.)

Psychosocial- Exposure therapy – has shown the most benefit

Novel methods - internet based- virtual reality

Age Development conditioned fears

Psychological Sx DSM-IV Corresponding d/o

0-6 months Fear of loss of caregiver - -

6-8 months Shyness with stranger Separation anxiety disorder

8m-3yrs Separation anxiety, fear of lightening, thunder, animals, nightmares

Crying, clinging, withdrawal, freezing

4-5 yrs Fear of death, dead people

GAD, Panic disorder

5-12yrs Nightmares,Fear of fantasy objects, animals, physical things- natural disasters, germs, getting a serious illness

Shyness, timidity Avoidant PD, Specific phobias. OCD

13-17 yrs Fear of inadequacy, performance, rejection by peers

Fear of negative evaluation

Overanxious disorder, social phobia

17-21 yrs Fear of personal loss, failing personal standards

Panic disorder, agoraphobia

Classified as “Other disorder of infancy and childhood” in DSM-IV-TR

Excessive anxiety beyond that expected for the child’s developmental level related to:

- Separation- Impending separation from attachment figure

NB Must be in children <18 yrs old, and lasting at least 4 wks.

Fear of social or performance situations due to anticipated scrutiny, humiliation or embarrassment

Exposure provokes anxiety/panic Considered excessive or unreasonable Situations avoided or endured with anxiety Significant interference or suffering Duration > 6 months if age < 18

Generalized or circumscribed

Epidemiology:- 6.8% of the population- Onset - by age 11, 50% have symptoms;

- by age 20, 80% have symptoms- Children – may refuse to go to school;

- Associated with early drop out from school

- Selective mutism – highly likely becomes

social anxiety disorder (severe variant)

Etiology-Familial, with recurrence risk ratio 2<x<6

i.e. Moderate heritability (chromosome 16 implicated –NE transporter)

- Heritable behavioural trait = behavioural inhibition (strong association)

Consequences:- Reduced work productivity- Financial costs- Reduced quality of life

Despite these issues – only half seek treatment, and usually after 15-20 years of suffering

ALCOHOL /SUBSTANCE ABUSE/DEPENDENCE- Strongly consider underlying social phobia in pts with a history of alcohol abuse/dependence» ¼ of pts may have comorbid abuse

Parkinsons pts – may frequently develop social anxiety – suggesting striatal involvement

Biopsychosocial approachBio – SSRIs* SNRIs* RIMAs+MAOI

sAntiCon BDZs

Escitalopram Venlafaxine Moclobemide Gabapentin Clonazepam

Fluvoxamine Phenelzine Pregabalin Alprazolam

Sertraline Divalproex Bromazepam

Paroxetine Topiramate

Citalopram

Fluoxetine

1st line: SSRI, SNRI2nd line: BDZ, AntiCon, MAOIs

Other alternatives with evidence of benefitAntidepressants AntipsychoticsBupropion (NDRI) OlanzapineMirtazapine (NaSSa) RisperidoneClomipramine (TCA) Quetiapine

Aripiprazole

Trigger

Perception of Danger

Increased Anxiety

- Escape- Avoidance- Safety behaviours

Reinforc

ement

Reduced Anxiety

Cognitive restructuring

Exposure therapy

Reinforcement

Beliefs & Assumptions

CBT - 12-15 sessions – lasting 50-90 minutes(individual or group therapy)

Correcting distorted cognitions – e.g. Everyone laughing at me – come up with alternative explanations

Exposure therapy – may be integrated in CBT- e.g. Returning item, going to crowded mall

Social skills training- making small talk, looking at tone, posture, active listening, assertiveness

Epidemiology- 3.1% of the population affected (F:M = 2:1)- Onset

(median US age=31 yrs, but often childhood)

- 25% have onset by 20 yrs old- 50% have onset b/w 20-47 yrs old

- Children- may be “overanxious disorder of

childhood”

Kessler RC et al. Arch Gen Psychiatry, 2005

Elderly – - may be associated with social isolation, trauma, migration, illness in spouse, bereavement- left untreated – may be associated with medical/psychiatric complications

- Cardio/cerebrovascular disease- COPD- Malnutrition- Depression- Dementia- Alcohol abuse

Weisberg R.B. J Clin Psychiatry, 2009

Etiology- Multiple neurotransmitters likely involved

- 5-HT, NE, CCK- Genetic factors likely involved

- Some twin studies – show 50% concordance rate in monozygotic twins, and 15% in dizygotic twins

- Behavioural, psychosocial factors involved

Excessive, wide-spread and uncontrollable anxiety and worry ( 6 months)

Symptoms of tension and exhaustion (3/6) restlessness, muscle tension, tiredness, irritability,

insomnia, difficulty concentrating NB – children only need ≥1

Worry not confined to another Axis I disorder

Significant distress or impairmentNot due to the effects of substance of GMC

Often – do not present with anxiety initially - May be

PainFatigueSleep disturbancesPoor concentrationDepression

- Frequently associated with disabilities in work, education, and/or social interactions

Comorbidities common – mood disorders, anxiety disorders, substance abuse

Biopsychosocial approach- Bio

SSRIs* SNRIs* TCAs AntiCon BDZs

Escitalopram* Venlafaxine* Imipramine Pregabalin Lorazepam

Alprazolam

Sertraline* Bromazepam

Paroxetine* Diazepam

Citalopram

1st line: SSRI, SNRI x 8-12 wks2nd line: BDZ, NDRI, Buspar, Pregabalin, TCA

Other alternatives with evidence of benefitAntidepressants AntipsychoticsBupropion (NDRI) OlanzapineMirtazapine (NaSSa) Risperidone

OtherBuspirone (Buspar)

With discontinuation of treatment- 20-40% relapse within 6-12 m, suggesting long term treatment is necessary

CBT – most evidence for efficacyEfficacy is comparable to pharmacologic

therapy, but may have higher remission ratesOther therapies that may be effective:

- Short term psychodynamic therapy- Interpersonal therapy

Trigger

Perception of Danger

Increased Anxiety

- Escape- Avoidance- Safety behaviours

Reinforc

ement

Reduced Anxiety

Cognitive restructuring

Exposure therapy

Reinforcement

Beliefs & Assumptions

Panic attacks (PA)Recurrent and unexpected, acute, time-limited

symptoms (at least 4/13)Not caused by substance or GMC

Anticipatory anxiety Concern about additional attacks, their implications

and consequences or change in behaviour 1 month

Agoraphobia Avoidance/distress/anxiety in places or situations

difficult to escape or get help in case of PA

Panic attacks – may come from a dysfunction of the fear circuitry

Amygdala – central involvement- Consists of several distinct nuclei in the brain

YohimbineLactateCO2CaffeineIsoproterenol5HT agonists (fenfluramine, m-CPP)Choleocystokinin (CCK-4, CCK-5)Stimulants – nicotine, amphetamines

Biopsychosocial approach- Bio

SSRIs* SNRIs* TCAs AntiCon BDZs

Escitalopram Venlafaxine Imipramine Gabapentin Lorazepam

Fluoxetine Clomipramine Divalproex Alprazolam

Sertraline

Paroxetine Diazepam

Citalopram Clonazepam

Fluvoxamine

1st line: SSRI, SNRI2nd line: BDZ, NaSSA, TCA3rd line: Anticon, MAOI, Atypical Antipsych, RIMA, pindolol

Other alternatives with evidence of benefitAntidepressants AntipsychoticsBupropion (NDRI) OlanzapineMirtazapine (NaSSa) Risperidone

QuetiapineOther: Pindolol

SSRI Benefits – may be seen within 1 wk;- up to 6-8 wks

Continued benefits may be seen after 12 m Treatment time of 8 -12 m is suggested, to

prevent relapse risk.

CBT – most evidence for efficacyEfficacy is comparable to pharmacologic

therapy, but may have higher remission ratesOther therapies that may be effective:

(BUT – INSUFFICIENT evidence to recommend)- Psychodynamic therapy- Eye Movement Desensitization and Reprocessing (EMDR)

Epidemiology- 1% of population (F:M= 3:2)- Onset – median age 19 yrs old, though can be childhood onset (NB – in childhood, F:M= 1:2)- Children

Etiology:- Dysregulation of 5-HT*- Genetics – significant

35% of 1st degree relatives of OCD also have OCD- Neuroimaging studies

- show increased metabolism of frontal lobes, caudate and cingulum

- Behavioural, psychosocial factors involved

Obsessions recurrent, persistent thoughts, urges or images

experienced as intrusive and anxiety-provoking, distinct from excessive worry, attempted to be suppressed, ignored or neutralizedcontamination, harm/aggression, somatic, religious, sexual

Compulsions repetitive, excessive behaviours or mental acts and

rituals aimed to prevent or decrease anxiety/distresscleaning, checking, counting, repeating, arranging, hoarding

Obsessions or compulsions are time consuming (>1 hr/day) or cause clinically significant distress

At some point – obsessions/compulsions are recognized as excessive or unreasonable(may not occur in childhood)

Not due to medical condition/substance

Obsessions – are distressing – e.g. Repeated thoughts about contamination

Usual response – compulsion – a behaviour aimed at reducing the anxiety associated with obsession – e.g. wash hands – temporary relief from anxiety of obsession, but then obsession returns.

Egodystonic: i.e. “alien”, not within his/her control BUT – recognized as product of the mind (i.e. Not thought insertion)

Children - clinical features:- Most frequent compulsion children

- Handwashing (75%)- Checking- Sorting

May not be egodystonic – often brought by parents

Small subset (<5%) – ass with Gp A β-hemolytic streptococcal infection (scarlet fever, “strep throat”) abrupt onset, with motor abnormalities = PANDAS (Paediatric Autoimmune Neuropsychiatric Disorder Ass with Streptococcal infection)

Elderly onset – more concerns about morality and washing rituals.

Comorbid issues with OCD“Depressing BODY TAASTE”:- Depressive disorder- Body dysmorphic disorder- Trichotillomania and other impulse control d/o- Anxiety Disorders- Autism- Schizophrenia- Tourette’s/Tic disorders- Eating Disorders e.g. Anorexia nervosa

Biopsychosocial- Bio

SSRIs* SNRIs* TCAs AntiCon AntiPsych

Escitalopram Venlafaxine Gabapentin Risperidone

Fluoxetine Clomipramine Topiramate Olanzapine

Sertraline IV Clomipramine

Quetiapine

Paroxetine Haloperidol

Citalopram

Fluvoxamine

1st line: SSRI2nd line: Clomipramine, SNRI, NaSSA, Risperidone3rd line: Something else....antipsych, anticon, MAOI

Dosages of meds e.g. SSRIs may need to be higher

Response may take 6 wks or longerMost recommendations – suggest staying on

treatment for 1-2 yrs (reduce relapse risk)

Neurosurgical options- deep brain stimulation - anterior cingulotomy- anterior capsulotomy,- subcaudate tractotomy- limbic leucotomy

Indicated for severe OCD, refractory to therapy/medications

40-60% of refractory pts may benefit

CBT with Exposure Response Prevention (ERP)- the most evidence for efficacy for treatment

Individual may be better than gp (individualization of treatment)

Anxiety is common – we all experience thisPathological anxiety can also be common, and

is not a sign of personal weakness.Important, but sometimes difficult to recognize. There are significant biological underpinnings to

anxiety disorders.Psychological approaches are very effective.Treatment can be very effective, but should be

tailored to individual patients.Use BIOPSYCHOSOCIAL approach.